Abstracts

Rationale: Eslicarbazepine acetate (ESL) is not approved for monotherapy use. Two identical phase III studies (093-045 and 093-046) suggest that conversion to ESL monotherapy is effective and well tolerated in patients with partial-onset seizures (POS) (Pazdera et al, Epilepsy Curr 2014;14[Suppl.1]:108; Sperling et al, Epilepsy Curr 2014;14[Suppl.1]:431−2). This analysis uses pooled data from these studies to determine the proportion of patients with improvements in seizure control during ESL monotherapy (1200mg and 1600mg once-daily [QD]). Methods: Studies 093-045 and -046 were 18-wk, randomized, double-blind, conversion-to-monotherapy studies which evaluated ESL 1200mg and 1600mg QD, compared with a historical control (as described by French et al, Epilepsia 2010;51:1936-43). Patients aged 16-70 years with POS not well controlled (≥4 POS in the 8 wks before screening, with no 4-wk seizure-free period) by 1-2 antiepileptic drugs (AEDs) were randomized (2:1) to ESL 1600mg or 1200mg QD (2-wk titration; 6-wk conversion [other AEDs withdrawn]; 10-wk monotherapy). The primary endpoint was the proportion of patients meeting ≥1 of 5 exit criteria (related to worsening of seizure control) by wk 16 (French et al, AES 2014). In both trials, seizure improvement endpoints (reduction in standardized seizure frequency [SSF] and seizure freedom) were prospectively specified as secondary endpoints. Results: Overall, 365 patients began ESL therapy (1600mg, n=242; 1200mg, n=123). Median age was 38 years; 52.1% were female. The pooled efficacy population (patients who began monotherapy conversion) comprised 332 patients (1600mg, n=218; 1200mg, n=114). For the 18-wk double-blind period there were improvements in SSF with both doses of ESL; median reductions vs baseline were 43.2% for ESL 1600mg and 35.7% for ESL 1200mg. The 50% responder (≥50% reduction from baseline in seizure frequency) rates were 43.1% and 36.0%, respectively. 8.7% and 7.9% of patients experienced seizure freedom (100% reduction in seizures) during the 10-wk ESL monotherapy period, and 15.6% and 14.9%, respectively, during the last 4 wks of the monotherapy period. There were improvements in seizure control with ESL monotherapy in patients with different categories of POS, in US patients and non-US patients (Table 1), and in patients who switched from various different baseline AEDs (Figure 1). Compared with patients who switched from carbamazepine or oxcarbazepine, more marked improvements in seizures occurred in patients who converted from other AEDs (Figure 1). Similar proportions of US and non-US patients had seizure freedom during the monotherapy period (US: 8.7% [ESL 1600 mg] and 6.8% [ESL 1200 mg]; non-US: 8.8% and 9.8%). Conclusions: Conversion to ESL monotherapy (1200mg and 1600mg QD) led to reductions in median seizure frequency in patients with POS not well controlled by 1−2 other AEDs. A substantial proportion of patients had ≥50% reduction in seizure frequency.